Flash Fabrication of Orally Targeted Nanocomplexes for Improved Transport of Salmon Calcitonin across the Intestine.

Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.

Efficacy and safety of elcatonin in postmenopausal women with osteoporosis: a systematic review with network meta-analysis of randomized clinical trials.

The present systematic review aimed to evaluate bone mineral density (BMD) change and complication rates of elcatonin on treating postmenopausal osteoporosis. The result confirmed efficacy of elcatonin and safety in combination therapies of elcatonin (C-E). INTRODUCTION: Postmenopausal osteoporosis is an important issue in global aging trends. One treatment of osteoporosis is elcatonin, a kind of calcitonin. However, it has been challenged for long time because of safety. Many trials investigated on this topic, but they were designed differently. Those designs can be categorized in monotherapy of elcatonin (M-E) and C-E. Unfortunately, no synthesized evidence dealt this topic. METHODS: This study systematically identified target trials from six important databases and only included randomized controlled trial for synthesis. Two investigators assessed quality of eligible trials using the Cochrane Risk of Bias Tool, and they independently extracted data. Network meta-analysis performed Peto odds ratio (POR, used for dealing with zero cell) or weighted mean difference (WMD, for continuous data) with 95% confidence intervals (CI) and consistency H. RESULTS: Sixteen trials recruiting 2754 women with postmenopausal osteoporosis were included in our study. Elcatonin therapies and non-elcatonin medications had comparable fracture rates and bone mineral density change. Yet, C-E (WMD, - 18.93; 95% CI, - 23.97 to - 13.89) and M-E (WMD, - 13.72; 95% CI, - 19.51 to - 7.94) had significantly lower pain score than non-elcatonin medications. However, M-E (POR = 8.413, 95% CI, 2.031 to 34.859) and non-elcatonin medication (Peto OR, 7.450; 95% CI, 1.479 to 37.530) had significantly higher complication rates than placebo. No evidence detected inconsistency and small study effect in this network model. CONCLUSIONS: Based on current evidence, C-E may be considered for treating postmenopausal osteoporosis because it benefits on pain relief and complications. Moreover, it shows comparable fracture rate and bone mineral density change as compared with anti-osteoporosis and calcium supplements. Nevertheless, further trials are needed to investigate formula and dosages of elcatonin.

Does salmon calcitonin cause cancer? A review and meta-analysis.

Recently an association between the use of calcitonin and cancer has been postulated. We reviewed the biological rationale and performed an additional analysis of historical data with respect to the possibility. An association cannot be excluded, but the relationship is weak and causality is unlikely. The purpose of the present study is to review the strength of association and likelihood of a causal relationship between use of calcitonin and cancer. We reviewed the evidence for this association, including the molecular signaling mechanisms of calcitonin, preclinical data, an "experiment of nature," and the results of a previous meta-analysis which showed a weak association. We performed an additional meta-analysis to incorporate the data from a novel investigational oral formulation of salmon calcitonin. Review of the literature did not identify a cellular signaling mechanism of action which might account for a causal relationship or toxicologic or postmarketing data to support the thesis. Additional clinical results incorporated into previous meta-analyses weakened but did not completely negate the possibility of association. A causal association between calcitonin use and malignancy is unlikely, as there is little biological plausibility. The preponderance of nonclinical and clinical evidence also does not favor a causal relationship.

Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P<0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin.

Individualizing osteoporosis medications.

CLINICAL SCENARIO: Mrs. JD is a 58-year-old postmenopausal woman having symptoms of hot flashes and night sweats. She has a dual-energy x-ray absorptiometry T-score of -2.4 in the femoral neck, consistent with low bone mass or osteopenia. She has a parental history of hip fracture. FRAX shows the 10-year absolute risk of major osteoporotic fracture equal to 18% and the 10-year risk of hip fracture above 3% at 3.2%, which meets the National Osteoporosis Foundation threshold. Mrs. JD is taking calcium 1,200 mg, between supplement and diet, and 1,000 IU vitamin D3 daily. How should she be treated?

Prevention of osteoporosis: one step forward, two steps back.

For many years, hormone replacement therapy (HRT) was the mainstay for osteoporosis prevention in postmenopausal women until a large randomized clinical trial raised serious safety concerns. This resulted in a big drop in HRT use and its demotion by regulatory authorities to second-line treatment. Many clinicians now feel that HRT is not safe to use, and recommend various alternatives for the treatment of osteoporosis. But how effective are these alternative therapies, are they any safer than HRT, and how do their costs compare? This review questions the validity of the safety concerns about HRT, and highlights the safety concerns about alternative therapies. It concludes that HRT is as safe as the other treatment options, and its efficacy and low cost demand that it be restored as a first-line treatment for the prevention of postmenopausal osteoporosis. Other therapies are available for use in osteoporosis, and the bisphosphonates are particularly effective for the treatment of the established disease. However, they must be used selectively and with caution, and are best restricted to those patients who are elderly or have severe disease. New treatments are emerging, but again caution must be taken until any long-term adverse effects have been identified.

Efficacy and harms of nasal calcitonin in improving bone density in young patients with inflammatory bowel disease: a randomized, placebo-controlled, double-blind trial.

OBJECTIVES: There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). The objective of this study was to establish the efficacy and safety of intranasal calcitonin in improving bone mineral density (BMD) in young patients with IBD and to define additional factors that impact bone mineral accrual. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial in 63 participants, ages 8-21 years, with a spinal BMD Z-score ≤ -1.0 s.d. measured by dual energy X-ray absorptiometry. Subjects were randomized to 200 IU intranasal calcitonin (n=31) or placebo (n=32) daily. All received age-appropriate calcium and vitamin D supplementation. Subsequent BMD measurements were obtained at 9 and 18 months. RESULTS: Intranasal calcitonin was well tolerated. Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract. The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the two therapeutic arms. In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)(calcitonin)=0.21 (0.37), ΔZSBMD(9-0)(placebo)=-0.15 (0.5), P=0.02); however, this was only a secondary subgroup analysis. Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort. Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity. Factors associated with lower bone mineral accrual rate were more severe disease-as indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulators-and higher daily caffeine intake. CONCLUSIONS: Intranasal calcitonin is well tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD. Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes. Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD.

Evaluation of symptomatic slow-acting drugs in osteoarthritis using the GRADE system.

BACKGROUND: Symptomatic slow-acting drugs (SYSADOA) have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA). METHODS: The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations. RESULTS: Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed. CONCLUSION: In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

Hypercalcemia and status epilepticus relates to salmon calcitonin administration in breast cancer.

Calcitonin is currently used to treat hypercalcemia of many clinical types. However, we encountered a woman who suffered severe hypercalcemia and status epilepticus, both of which developed 8 days after the administration of salmon calcitonin for the treatment of breast cancer. When the patient first presented her serum calcium level was 15.5mg/dl, intact parathyroid hormone level 118 pg/ml, calcitonin <2 pg/ml, magnesium 1.2mg/dl, and phosphate 1mg/dl. Her serum calcium level returned to the reference range within 48 h after correction. At follow-up no hypercalcemia had developed, although the patient had received no further treatment for her breast cancer and multiple metastases were subsequently detected. Her hypercalcemia is ascribed to exogenous calcitonin supplementation. These conflicting events may be due to functionally heterogeneous calcitonin receptors or to activation of 1 alpha-hydroxylase by exogenous calcitonin.

Safety and efficacy of a novel salmon calcitonin (sCT) technology-based oral formulation in healthy postmenopausal women: acute and 3-month effects on biomarkers of bone turnover.

UNLABELLED: Oral administration of calcitonin could improve compliance to long-term treatment. Efficacy and safety of a novel oral formulation was assessed on 277 postmenopausal women. The results show (1) effective enteral absorption, (2) marked inhibition of bone resorption with minimal alteration of formation, and (3) reproducibility of responses over 3 months. INTRODUCTION: We have recently introduced an Eligen technology-based oral formulation of salmon calcitonin (sCT) that effectively delivers the hormone to the circulation. The efficacy and safety during longer-term administration, however, has not been investigated in the target population. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging clinical trial including 277 healthy postmenopausal women 55-85 years of age. Women received treatment with either daily (0.15, 0.4, 1.0, or 2.5 mg) or intermittent doses (1.0 mg, every other day) of sCT combined with the delivery agent (8-[N-2-hydroxi-5-chloro-benzoyl]-amino-caprylic acid, 200 mg) or placebo for 3 months. All participants received 1,000 mg calcium plus 400 IU vitamin D daily throughout the study. Efficacy parameters were the acute and/or pre-dose changes in serum and urinary C-terminal telopeptide of type I collagen (CTx), N-mid osteocalcin (OC), bone-specific alkaline phosphatase (BSALP), calcium, and parathyroid hormone (PTH) measured by established immunoassays. RESULTS: After the first dose, sCT evoked dose-dependent decreases in serum CTx (-60.8% to -81.8% from baseline) compared with placebo, reaching nadirs 2-3 h after drug intake, after which, gradual increases were observed. The simultaneous acute changes in OC were statistically nonsignificant. Area under the curve (AUC) of serum CTx responses at months 1 and 3 showed strong correlation with those at baseline (both r = 0.78, p < 0.001). At month 3, the placebo-corrected changes in the pre-dose value of serum and urinary CTx were significant only in the 1.0-mg dose group (-18.9% and -20.5%, respectively, p < 0.05). The placebo-corrected change in OC was -8.6 (p = 0.09), whereas the change in BSALP was -7.3 (p = 0.02). The oral formulation was well tolerated, with mild to moderate gastrointestinal and skin manifestations apparent mainly in the high-dose groups. CONCLUSION: The results of this 3-month trial show that the novel Eligen technology-based oral formulation of sCT has potential to become a safe and effective treatment for postmenopausal bone loss. Future trials are needed to assess the impact of long-term administration on changes in BMD and fracture risk.

A placebo controlled crossover trial of subcutaneous salmon calcitonin in the treatment of patients with fibromyalgia.

The objective of this study was to evaluate the relative efficacy and tolerability of subcutaneously (s.c.) administered salmon calcitonin (sCT) in the treatment of patients with fibromyalgia. Eleven patients who fulfilled the American College of Rheumatology classification criteria for fibromyalgia were studied in a double-blind, crossover trial in which they alternatively received salmon calcitonin (100 IU s.c.) and isotonic saline (1 cc s.c.) for four weeks, with a four weeks wash-out period between the treatments. None of the 11 outcomes measures (seven analog scales, dolorimetry score, and three SIP scores) showed a significant improvement with sCT. The principal side effect observed with sCT was nausea in ten patients and erythema in four patients. These data suggest that sCT given at a dose of 100 IU daily for one month is not effective in the treatment of fibromyalgia.

Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women.

The objectives of this study were to determine whether cyclic administration of recombinant human GH, with or without the antiresorptive agent, salmon calcitonin (CT), provides clinically meaningful increases in bone mineral density (BMD) at the lumbar spine and proximal femur in postmenopausal osteopenic women. The design of the study was a randomized clinical trial consisting of 12 56-day treatment cycles. Each cycle was initiated by a 12-day period of hormone administration, followed by 44 days of supplemental calcium only. Cycles of hormone administration consisted of 7 daily injections of recombinant GH (20 micrograms/kg.day) or its placebo, followed by 5 daily injections of salmon CT (100 U/day) or its placebo. The study was performed at the Palo Alto Veterans Affairs medical center. The patients were 84 healthy women with lumbar spine BMD more than 1 SD below the average value for a healthy 25-yr-old Caucasian woman. BMD was measured at the lumbar spine and proximal femur by dual energy x-ray absorptiometry. Biochemical markers of bone turnover and circulating insulin-like growth factor I were also measured. GH treatment increased insulin-like growth factor I concentrations from low values at baseline (112 +/- 56 ng/mL) to the young normal range (approximately 430 +/- 125 ng/mL). Groups receiving GH plus CT or GH plus placebo increased lumbar spine BMD at 2 yr by 2.70 +/- 0.81% (P < 0.01) and 1.72 +/- 0.74% (P < 0.05; intention to treat analysis). No significant change occurred in women receiving placebo plus CT or combined placebo. Significant increases in total hip BMD of 1-2% were observed for the GH plus placebo and placebo plus CT groups, with a nonsignificant trend in the GH plus CT group. For the femoral trochanter, significant increases were observed in the GH plus CT and placebo plus CT groups only. No significant change in femoral neck BMD was observed in any group. Women taking replacement estrogen had the same BMD response as those who were estrogen deficient. No significant increase in BMD was observed between 24 and 36 months in the 62 women who returned for a 3 yr measurement. In response to GH, short term increases in resorption and formation markers were observed, but these had decreased before the next treatment cycle. No long term changes in resorption markers were observed, but women in the GH groups showed a sustained rise in circulating osteocalcin over the entire 2-yr protocol. GH given cyclically with or without CT for 2 yr achieved statistically significant increases in BMD of the lumbar spine and selected areas of the hip in postmenopausal women. These gains were less marked than those achieved with estrogen or bisphosphonates and were associated with a relatively high incidence of adverse experiences. Therefore, it is unlikely that cyclic GH with or without CT will prove clinically useful in the treatment of postmenopausal women with osteoporosis.

Patient responsiveness to calcitonin salmon nasal spray: a subanalysis of a 2-year study.

A subanalysis of results from a randomized, double-blind, placebo-controlled, parallel-group, 2-year study was conducted to evaluate the response of individual patients to therapy with 200 IU/d calcitonin salmon nasal spray compared with placebo in postmenopausal women who had low bone mass. All patients received 500 mg/d of oral supplemental calcium. A response to therapy was defined as an increase from baseline in lumbar vertebral bone mineral density, measured by use of dual-energy x-ray absorptiometry, at the end of 2 years of treatment. Of 41 valid completers (ie, patients who met the entry criteria, were compliant with the protocol, and completed the study) treated with calcitonin salmon nasal spray, 31 (76%) responded positively to treatment. Of 40 valid completers who received placebo, 25 (63%) lost bone mass (P = 0.001 between groups). The relative risk of bone loss for patients receiving calcitonin salmon nasal spray was 0.19 (95% confidence interval, 0.07 to 0.50), representing an 81% risk reduction. This subanalysis demonstrates that the benefits of calcitonin salmon nasal spray therapy were seen in the majority of women studied. Calcitonin salmon nasal spray represents an effective therapeutic alternative for osteoporotic women more than 5 years postmenopause who reject or cannot tolerate estrogens or for whom estrogens are contraindicated.

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: a dose-response study.

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to -0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P < 0.05-0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P = 0.030-0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P = 0.022-0.003). The biochemical parameters of bone turnover revealed decreases of 10-20% (P < 0.001; within group testing) in the groups treated with the two highest sCT doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of postmenopausal osteoporosis with continuous daily oral alendronate in comparison with either placebo or intranasal salmon calcitonin.

Alendronate sodium (ALN) is a potent amino bisphosphonate which specifically inhibits osteoclastic bone resorption and has been found to reverse bone loss in several animal models. To determine if daily oral ALN treatment could prevent or reverse bone loss in osteoporotic postmenopausal women, and to compare ALN to intranasal salmon calcitonin (CT), a 2-year, double-masked, randomized, placebo-controlled study was initiated at 9 clinical centers in Italy. Two hundred and eighty six postmenopausal women (age 48-76) with spinal bone mineral density (BMD) > or = 2 SD below adult mean peak, with or without vertebral crush fractures, were randomized to one of four treatment arms: ALN 10 mg daily, ALN 20 mg daily or matching placebo (these groups all double-masked), or CT 100 IU daily (open label) for 2 years. All patients received supplemental calcium (as carbonate) 500 mg daily. Bone mass was measured by dual-energy X-ray absorptiometry of the PA lumbar spine (LS) and proximal femur (femoral neck and trochanter) at 6-month intervals. Subject safety was measured through sequential clinical and laboratory evaluation. A planned 1-year interim analysis of this ongoing study was performed centrally in a manner that maintains the double-mask for all subjects receiving oral study drug. Relative to PBO, ALN at either 10 mg or 20 mg daily increased LS BMD by 4.7% and 6.1%, respectively; each increased femoral neck BMD by 3.1% and increased trochanter BMD by 3.3% and 3.8% respectively. In contrast, CT failed to significantly increase BMD of either the spine, femoral neck or trochanter, either relative to baseline or to PBO.(ABSTRACT TRUNCATED AT 250 WORDS)

Salmon calcitonin induces pituitary tumor in rats.

Calcitonin is widely used in the treatment of post-menopausal osteoporosis. The present study was designed to investigate the effects of salmon calcitonin (SCT) on the incidence of the pituitary tumors in Sprague-Dawley (SD) rats. Subcutaneous injections of SCT at a dose of 160 IU/kg/day for 6 months reduced body weight and induced one pituitary hyperplasia and three pituitary adenomas in 4 of 5 animals, while 5 controls did not show any changes. Prolactin-positive cells were located at the periphery of the affected pituitaries adjacent to the prolactin-negative adenomas. In addition, serum concentrations of prolactin and TSH were lower than in the controls, although serum calcium or LH levels were not significantly different from the controls. Among 7 animals treated with SCT for 6 months followed by no medication for another 6 months, 5 adenomas were detected, one of which had invasive growth toward the adjacent tissue, whereas only one adenoma was found in 9 controls. These results suggest that SCT administration at a high dose may induce the formation of pituitary adenoma, or may accelerate the development of spontaneous pituitary adenomas, some of which show frequent mitotic figures and invasive growth into the surrounding tissue, possibly resulting in malignant transformation. This indicates the need for caution in considering whether calcitonin injections into patients with osteoporosis as well as Paget's disease may induce such pituitary tumors.

[Treatment of primary osteoporosis with calcium and salmon calcitonin]. / Behandlung der primären Osteoporose mit Calcium und Lachscalcitonin.

Fifty-nine consecutive patients (19 men, 40 women, mean age 60.8 [27-80] years) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin. All the patients were given 1 g calcium by mouth every morning. Group 1 (n = 20) received no other specific medication while group 2 (n = 19) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 (n = 20) received the same dose every evening. The pain reported by the patients was subdivided into four severity grades, and analgesic consumption was recorded. In group 1 there was a nonsignificant decrease in pain, but in groups 2 and 3 there was a highly significant diminution in pain (P less than 0.005) and in analgesic intake (P less than 0.01). Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5% increase in the distal radius in group 2 (P = 0.0001) and a 7.1% increase in group 3 (P = 0.0001), while in group 1 mineral content had decreased by 4.3% (nonsignificant). These results show that a significant gain in bone mass can be achieved by administration of calcitonin, either daily or on alternate days. The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1.

Treatment of steroid-induced osteopenia with calcitonin in corticosteroid-dependent asthma. A one-year follow-up study.

Sixty-two steroid-dependent asthmatics who had not received any form of treatment to prevent bone loss were studied during a 12-month period. Patients were randomly divided into two groups. Thirty-one patients were treated with 1 g of elemental calcium taken daily plus 100 IU of salmon calcitonin every other day, administered subcutaneously; the remaining 31 patients received only calcium supplementation. In the calcitonin group, 11 patients dropped out of the study because of severe side effects (seven patients), lack of compliance (three patients), and exacerbation of asthma (one patient). The 20 patients who completed the 12-month follow-up period were analyzed and compared with 20 sex-matched patients from the control group. At one year, bone mineral density (BMD) had increased in the calcitonin group by a mean of 4% (p less than or equal to 0.001), whereas in the control group BMD had decreased by 2.5% (p less than or equal to 0.05). Parameters of bone remodeling (alkaline phosphatase and osteocalcin) decreased significantly in the calcitonin-treated group but not in the control group. Our findings show that calcitonin 100 IU, given three times/wk, is an effective drug in the treatment of steroid-induced osteopenia. Side effects, however, are frequent and cause a high degree of dropout from therapy. These findings suggest that further studies should be carried out with lower doses of calcitonin or by other better tolerated forms of delivery such as in a nasal spray.